Abstract
The fine control of inflammation following injury avoids fibrotic scars or impaired wounds. Due to side effects by anti-inflammatory drugs, the research is continuously active to define alternative therapies. Among them, physical countermeasures such as photobiomodulation therapy (PBMT) are considered effective and safe. To study the cellular and molecular events associated with the anti-inflammatory activity of PBMT by a dual-wavelength NIR laser source, human dermal fibroblasts were exposed to a mix of inflammatory cytokines (IL-1β and TNF-α) followed by laser treatment once a day for three days. Inducible inflammatory key enzymatic pathways, as iNOS and COX-2/mPGES-1/PGE2, were upregulated by the cytokine mix while PBMT reverted their levels and activities. The same behavior was observed with the proangiogenic factor vascular endothelial growth factor (VEGF), involved in neovascularization of granulation tissue. From a molecular point of view, PBMT retained NF-kB cytoplasmatic localization. According to a change in cell morphology, differences in expression and distribution of fundamental cytoskeletal proteins were observed following treatments. Tubulin, F-actin, and α-SMA changed their organization upon cytokine stimulation, while PBMT reestablished the basal localization. Cytoskeletal rearrangements occurring after inflammatory stimuli were correlated with reorganization of membrane α5β1 and fibronectin network as well as with their upregulation, while PBMT induced significant downregulation. Similar changes were observed for collagen I and the gelatinolytic enzyme MMP-1. In conclusion, the present study demonstrates that the proposed NIR laser therapy is effective in controlling fibroblast activation induced by IL-1β and TNF-α, likely responsible for a deleterious effect of persistent inflammation.
Highlights
IntroductionAny injury or infection triggers an inflammatory reaction via cytokines deriving from platelet degranulation and pathogen-associated molecular patterns
The human dermal fibroblasts Normal human dermal fibroblasts (NHDF) have been treated with a mix of cytokines (IL-1β and tumor necrosis factor-α (TNF-α), each at 10 ng/mL) for 24 h and 48 h, the occurrence of inflammatory features depending on the exposure time has been evaluated
IL-1β and TNF-α have been used jointly to induce a pro-inflammatory phenotype in dermal fibroblasts, with the aim to investigate if photobiomodulation therapy (PBMT) delivered via a dual-wavelength NIR laser system (MLS-MiS) was effective in counteracting cell inflammatory response and modulating fibroblast functions involved in stromal activation, wound healing, and its alterations, which can lead to chronic ulcers or fibrosis
Summary
Any injury or infection triggers an inflammatory reaction via cytokines deriving from platelet degranulation and pathogen-associated molecular patterns. In both cases, damaged cells release reactive oxygen species and non-specific factors which contribute to activate the inflammatory response in cells of the innate immune system, fibroblasts, and epithelial and endothelial cells [1]. The correct progression of any acutely occurring inflammatory reaction is a key factor in the path leading to successful healing, which consists in repair/regeneration of damaged tissues and function recovery. Conditions of tissue stress or altered function can induce an adaptive response, known as parainflammation or low grade chronic inflammation, which is an intermediate condition between basal homeostasis and acute inflammation, and is associated with serious diseases, including obesity, diabetes, atherosclerosis, asthma, and neurodegenerative diseases [4]
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